Project Summary Epigenetic regulators often lie downstream of signaling pathways that culminate in post-translational modifications, which affect their activity and ensure appropriate transcriptional responses to developmental and environmental cues. Our preliminary studies indicate that an interaction between epigenetic regulator, TET3, and an X-linked, post-translational modification enzyme, OGT, may be central in detecting X chromosome dosage and poising cells for X-inactivation. We propose to investigate the role of the TET3-OGT interaction in regulation of X chromosome inactivation, to obtain molecular insight into how cells count X chromosomes.